Early colorectal cancers provide new evidence for a Lynch Syndrome-to-CMMRD Phenotypic Continuum
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Title: | Early colorectal cancers provide new evidence for a Lynch Syndrome-to-CMMRD Phenotypic Continuum |
Author: | Fernández Rozadilla, Ceres Álvarez Barona, Miriam Schamschula, Esther Bodo, Sahra López Novo, Anael Dacal, Andrés Calviño Costas, Consuelo Lancho, Angel Amigo Lechuga, Jorge Bello, Xabier Cameselle Teijeiro, José Manuel Carracedo Álvarez, Ángel María Colas, Chrystelle Muleris, Martine Wimmer, Katharina Ruiz Ponte, Clara |
Affiliation: | Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría |
Subject: | Lynch syndrome | CMMRD | Phenotypic continuum | Genetic modifiers | Whole-exome sequencing | |
Date of Issue: | 2019 |
Publisher: | MDPI |
Citation: | Fernández-Rozadilla, C.; Alvarez-Barona, M.; Schamschula, E.; Bodo, S.; Lopez-Novo, A.; Dacal, A.; Calviño-Costas, C.; Lancho, A.; Amigo, J.; Bello, X.; Cameselle-Teijeiro, J.M.; Carracedo, A.; Colas, C.; Muleris, M.; Wimmer, K.; Ruiz-Ponte, C. Early Colorectal Cancers Provide New Evidence for a Lynch Syndrome-to-CMMRD Phenotypic Continuum. Cancers 2019, 11, 1081 |
Abstract: | Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome, caused by heterozygous mutations in the mismatch repair (MMR) genes. Biallelic mutations in these genes lead however, to constitutive mismatch repair deficiency (CMMRD). In this study, we follow the diagnostic journey of a 12-year old patient with CRC, with a clinical phenotype overlapping CMMRD. We perform molecular and functional assays to discard a CMMRD diagnosis then identify by exome sequencing and validation in a cohort of 134 LS patients, a candidate variant in the MLH1 UTR region in homozygosis. We propose that this variant, together with other candidates, could be responsible for age-of-onset modulation. Our data support the idea that low-risk modifier alleles may influence early development of cancer in LS leading to a LS-to-CMMRD phenotypic continuum. Therefore, it is essential that larger efforts are directed to the identification and study of these genetic modifiers, in order to provide optimal cancer prevention strategies to these patients. |
Publisher version: | https://doi.org/10.3390/cancers11081081 |
URI: | http://hdl.handle.net/10347/21176 |
DOI: | 10.3390/cancers11081081 |
E-ISSN: | 2072-6694 |
Rights: | © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
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